3. Umpierrez GE et al. J Clin Endocrinol Metab . 2002;87:978-982. Hyperglycemia Is an Independent Marker of Inpatient Mortality in Patients With Undiagnosed Diabetes In-hospital Mortality Rate (%) Newly Discovered Hyperglycemia Patients With History of Diabetes Patients With Normoglycemia P < 0.01 P < 0.01
4. Postoperative Glycemic Control Correlates With Cardiac-Related Mortality * ( P <.001). Furnary AP et al. J Thorac Cardiovasc Surg . 2003;125:1007-1021. Mortality (%) 0.9 1.3 2.3 4.1 6.0 14.5 Average Postoperative Glucose (mg/dL) * * * *
5. Poor Outcomes Correlate With Hyperglycemia After Acute Ischemic Stroke Williams LS et al. Neurology . 2002;59:67-71. Blood Glucose at Admission .015 .07 .15 .018 .009 7.2 ± 0.4 73% 7% 10% 18% 6 ± 0.3 79% 5% 5% 11% Length of stay Discharged to home In-hospital mortality 30-Day mortality 1-Year mortality P value BG 130 mg/dL (n=258) BG <130 mg/dL (n=385) Outcome
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7. Hyperglycemia and Poor Outcomes Following Myocardial Infarction Arch Intern Med. 2009;169(5):438-446 In Hospital Mortality (%) Average Post-admission Glucose
11. Insulin and Sternal Wound Infections Furnary AP et al. Ann Thorac Surg . 1999;67:352-362. 4 3 2 1 0 DSWI (%) 87 88 89 90 91 92 93 94 95 96 97 Year CII Patients with diabetes Nondiabetic patients
12. Insulin and Mortality in CABG patients CII Year Furnary AP Endocr Pract . 2004;10(suppl 2):21-33. Mortality
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14. Intensive Insulin in the Critically Ill Van den Berghe G et al. N Engl J Med. 2001;345:1359-1367. 100 96 92 88 84 80 0 0 20 40 60 80 100 120 140 160 Intensive treatment Conventional treatment Intensive treatment Conventional treatment Survival in ICU (%) 100 96 92 88 84 80 0 0 50 100 150 200 250 In-Hospital Survival (%) Days After Admission Days After Admission 42.5% reduction in mortality with intensive treatment; P <.04 34% reduction in mortality with intensive treatment; P <.01
15. Benefits of IV Insulin Treatment in Critically Ill Hospitalized Patients Van den Berghe G et al. N Engl J Med. 2001;345:1359-1367. Reduction (%) 34% 46% 41% 50% 44%
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17. Stamford Project: Improvement in Mortality * *P <.01 compared with control group. † P <.05 compared with control group. † * † Krinsley JS. Mayo Clin Proc . 2004;79:992-1000. Decrease in Mortality With Treatment (%)
18. Leuven II- Intensive Insulin in MICU Patients with expected LOS >3 days Van den Berghe G et al. N Engl J Med. 2006;354;5:449-61 . * p<.05 * * *
22. How do we use this data to care for our patients?
23. American Diabetes Association 2009* “Standards of Medical Care” Diabetes Care 2009 32;Supp 1:S14-61 Circulation 2008;117;1610-19 Critical Care Med 2008 35:296-327 International Guidelines for Management of Severe Sepsis and Septic Shock: 2008 American Heart Association: Hyperglycemia and Acute Coronary Syndrome The Endocrine Society- Position Statement March 2009 * ADA/AACE statement March 09 promised new guidelines and recommended targets similar to the “conventional” arm of NICE-SUGAR <150 mg/dL 2C Critical E (Expert Consensus) <180-200mg/dL <126 mg/dL Noncritical <140 110 mg/dL Non-Fasting C A Evidence level <140 Critical non-surgical 110 mg/dL Critical surgical Fasting Patients <180 mg/dL 90-140 mg/dL C C Noncritical Critical <144-180 mg/dL Critical
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28. Source of Nutrition- Effects on Insulin Secretion Prandial insulin B L D B L D Basal insulin Basal insulin Basal insulin Prandial insulin The Eating Patient Pt. Receiving Continuous Feeds
31. Mimicking Nature With Insulin Basal/Bolus Concept Physiologic Insulin Secretion Insulin (µU/mL) Glucose (mg/dL) 9 B L D 150 100 50 0 7 8 9 10 11 12 1 2 3 4 5 6 7 8 AM PM Time of Day Basal glucose Adapted from Bergenstal RM et al. In: DeGroot LJ, Jameson JL, eds. Endocrinology. 4th ed. Philadelphia, Pa: WB Saunders Co.; 2001:821 50 25 0 24-hr profile Basal insulin
32. Basal-Bolus Insulin Therapy: Insulin Glargine at HS and Mealtime Lispro or Aspart Insulin aspart/glulisine/lispro Insulin glargine B D L HS Insulin Effect Adapted from Leahy J. In: Leahy J, Cefalu W, eds. Insulin Therapy . New York, NY: Marcel Dekker Inc.; 2002:87
33. Example: Patient’s Total Daily Insulin Estimate=60 Units 10 units aspart glulisine lispro 10 units aspart glulisine lispro 10 units aspart glulisine lispro 30 units glargine Insulin Effect Adapted from Leahy J. In: Leahy J, Cefalu W, eds. Insulin Therapy . New York, NY: Marcel Dekker Inc.; 2002:87
35. Example: Patient’s Total Daily Insulin Estimate=60 Units 13 units NPH 27 units NPH 40 units of insulin in the a.m. 20 units of insulin in the p.m. +13 units regular +7 units regular
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37. Insulin Requirement During Continuous Dextrose, TPN or Enteral Feedings, or Negligible Carbohydrate Exposure 8 12 6 10
38. Regimens for patient while NPO, on IV’s, or receiving continuous enteral feedings.
Review of 2030 consecutive patients admitted to Georgia Baptist Med Center. Hyperglycemic patients were classified as known DM or no hx of DM.
Pomposelli studied 100 uninfected adults undergoing elective surgery
Review of 7820 patients with Acute MI and admission glucose >140
Greater than 100 studies related to neutrophil function Decreased chemotaxis, phagocytosis, bacterial killing, decreased extravasation
First group was from 1987-91 and second group from sept 91- november 1997 Study done in Portland Oregon The average difference in glucose concentration between the two groups is approximately 25 points. First group was from 1987-91 and second group from sept 91- november 1997 Study done in Portland Oregon The average difference in glucose concentration between the two groups is approximately 25 points.
First group was from 1987-91 and second group from sept 91- november 1997 Study done in Portland Oregon The average difference in glucose concentration between the two groups is approximately 25 points. First group was from 1987-91 and second group from sept 91- november 1997 Study done in Portland Oregon The average difference in glucose concentration between the two groups is approximately 25 points. First group was from 1987-91 and second group from sept 91- november 1997 Study done in Portland Oregon The average difference in glucose concentration between the two groups is approximately 25 points. 19 of 968 in the first group vs. 12 of 1499 in the second group Number needed to treat = 100 During the same period of time, the rate of sternal wound infections in non-diabetics remained stable suggesting that the difference seen in this study is due to the implementaion of the infusion
87-91 sliding scale less than 200. 1991-96 target glucose range 150-20 199 125-175 2002 lowered to100-150. 1996 Protocol expanded to intra-op and continuation for 3 days.
Study done in 1 ICU in Belgium Hypoglycemia- (glucose less than 40 occurred in 39 patients in intensive group an 6 in the conventional group. No hemodynamic effects or convulsions.
Treatment of sepsis with activated protein C reduces mortality by 20% at 28 days. With a 3.4% risk of major bleeding and a cost of 10K per dose. Insulin cost .02 per unit. At 50 units daily equals $1 per day.
Acute Renal Failure= renal failure requiring dialysis Transfusions= number of transfusions per patient
Baseline group from 9/23/02-1/31/03- Treatment group 2/1/03-1/10/04
1200 patients randomized40% in the conventional group vs. 37.3% in the treatment group (p=.33) ICU for 3 days was reduced from 52.5% to 43% (p=.009) Hypoglycemia (glucose <40) increased from 3.1% of patients to 18.7%
Decrease in septicemia was limitied to surgical patients Mortality in surgical very tight Group 1 (1 st 2 studies) moderate <150 Mortality in Medical Group 2 (very tight 1 st 4 studies) Moderate <150 Mortality in Med surg
Slide 50 Twice-Daily Split-Mixed Regimens Twice-daily mixtures of NPH and regular insulins have been widely used for type 2 diabetes for many years Patient profiles of insulin levels shown in this slide do not come close to matching the normal endogenous secretory pattern seen in the shaded background Dawn phenomenon refers to the early morning fall of tissue insulin sensitivity counteracted by increased insulin secretion in nondiabetic individuals but manifested as rising glycemia in diabetic patients In some patients with marked dawn phenomenon, NPH insulin may be beneficial. Early morning hyperglycemia may also be managed by dividing the dose of NPH insulin between dinner and bedtime 1. Berger M et al. Diabetes Care . 1999;22(suppl 3):C71 2. Edelman SV, Henry RR. Diabetes Reviews . 1995;3:308
Slide 49 Mimicking Nature With Insulin Therapy Basal/Bolus Concept When considering glucose control, the focus must be on both postprandial and basal requirements. This slide illustrates the normal diurnal physiologic response, which highlights the need for both basal and meal insulin Meal-insulin release occurs in response to nutrient ingestion Basal insulin is continually secreted over a 24-hour period In the past, insulin formulations did not have adequate pharmacokinetics to duplicate these profiles. However, within the past few years, new insulin analogs have been developed that provide more physiologic profiles 1. Bergenstal RM et al. In: DeGroot LJ, Jameson JL, eds. Endocrinology. 4th ed. Philadelphia, Pa: WB Saunders Co.; 2001:821
Slide 61 Basal-Bolus Insulin Therapy: Insulin Glargine at HS and Mealtime Lispro or Aspart The slide depicts the profile of a “basal-bolus insulin” regimen, with insulin glargine at bedtime (HS) providing the basal component and prandial insulin lispro or insulin aspart providing the bolus component This regimen affords the following advantages: Provides flexibility for varying dietary habits Less risk of nocturnal hypoglycemia due to the 24-hour near-constant effect of insulin glargine, making it an ideal basal insulin Less risk of between-meal hypoglycemic episodes due to the short duration of the rapid-acting insulin analogs, which may also provide insulin coverage for snacks or extra meals with additional injections Avoidance of mixing different insulin preparations in the same syringe as single insulins are administered with each injection. Insulin pens are suggested for maximal convenience and accuracy in dosing 1. Leahy J. In: Leahy J, Cefalu W, eds. Insulin Therapy . New York, NY: Marcel Dekker, Inc.; 2002:87
Slide 50 Twice-Daily Split-Mixed Regimens Twice-daily mixtures of NPH and regular insulins have been widely used for type 2 diabetes for many years Patient profiles of insulin levels shown in this slide do not come close to matching the normal endogenous secretory pattern seen in the shaded background Dawn phenomenon refers to the early morning fall of tissue insulin sensitivity counteracted by increased insulin secretion in nondiabetic individuals but manifested as rising glycemia in diabetic patients In some patients with marked dawn phenomenon, NPH insulin may be beneficial. Early morning hyperglycemia may also be managed by dividing the dose of NPH insulin between dinner and bedtime 1. Berger M et al. Diabetes Care . 1999;22(suppl 3):C71 2. Edelman SV, Henry RR. Diabetes Reviews . 1995;3:308
1. 2. Norhammer followed 197 consecutive non-diabetics and found a relative risk of 1.95 (p<.001) of non-fatal reinfarction-
Brief Description of Various Protocols Malmberg K. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group. BMJ. 1997;314(7093):1512–1515. van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;345:1359–1367. Markovitz LJ, Wiechmann RJ, Harris N, et al. Description and evaluation of a glycemic management protocol for patients with diabetes undergoing heart surgery. Endocr Pract. 2002;8:10 –18. Goldberg PA, Siegel MD, Sherwin RS, et al. Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit. Diabetes Care. 2004;27:461–467.